Skye Bioscience, Inc.

Hello, and thank you all for participating in today's call. Joining me today is Puneet Dhillon, Sky's President and CEO, Chris Twitty, CSO, and Caitlin Arsenault, Sky's CFO. Before we begin, I'd like to caution that comments made during this conference call will contain forward-looking statements under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Sky's expectations regarding its development activities, timelines, and milestones. forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely, and reported results should not be considered as an indication of future performance. These forward-looking statements speak only as of today's date, and the company undertakes no obligation to revise or update any statements made today. I encourage you to review all the company's filings with the Securities and Exchange Commission concerning these and other matters. I'll now turn the call over to Puneet Gillan.

Good afternoon and thank you for joining us. I'm here with members of our management team to review Sky's first quarter 2025 performance. I'll briefly recap our key upcoming clinical milestones and highlight our operational roadmap for the rest of 2025 before turning it over to our CSO and CFO to share more details around our preclinical data and financials. We delivered meaningful scientific, clinical, and operational progress this quarter. Most notably, we completed enrollment in our Phase 2a CBON trial ahead of schedule. We've now moved forward with an amendment to extend the study to 52 weeks. This positions us to collect longer-term data on safety, tolerability, and efficacy, both as monotherapy and in combination with GLP-1. Lastly, we generated compelling new preclinical data that further validates the potential of namazumab as a weight loss therapy. Nemazumab continues to stand out with a differentiated mechanism that is distinct from both peripherally restricted small molecule CB1 inhibitors and GLP-1 agonists. Importantly, our recent preclinical studies demonstrated a truly peripherally restricted antibody like Nemazumab can potentially result in significant weight loss similar to a less restricted small molecule. And Nemazumab has the potential to provide additive weight loss to an incretin memetic like trisepatides. Later, our CSO, Dr. Chris Twitty, will discuss this new data in more detail. These findings reinforce our belief that namazumab has the potential to deliver durable weight loss with fewer safety concerns. We'll present additional data, including mechanistic and combination findings, at key scientific and investor events this year, starting with ECHO next week and ADA in June. Clinically, we are on track. Patients continue to receive treatment The Data Safety Monitoring Committee has completed three reviews with no safety concerns. That engagement remains high. Based on this progress, we expect to report top line weight loss data for the 26-week primary analysis of CBEYOND in late Q3 or early Q4. Before I pass it on, I want to address one topic proactively, the evolving policy environment. While our focus remains on disciplined execution, we're operating in a period of regulatory uncertainty marked by potential shifts in drug pricing policy and a lack of clear direction from federal healthcare leadership. Ongoing transitions at the FDA and NIH raise important questions about how innovation will be balanced with regulatory oversight in the years ahead. At Sky, we've assessed our exposure and believe it's limited in the near term as we prioritize our clinical development milestones. We're on track and we're tracking developments carefully. and we have preserved flexibility in our supply chain and capital deployment planning. Kate will speak more to how we've accounted for these variables in our financial outlook. Overall, we feel that we're in a solid position to move forward with the next stages of the Massimabs development lifecycle, and that we're uniquely positioned to help address the chronic nature of obesity and the need for sustainable long-term solutions. Chris, over to you.

Thank you, Penny. I'm pleased to share our thoughts on a few recent preclinical studies with the MathMath, a novel antibody-based, peripherally-restricted CB1 inhibitor. These studies were designed to not only address the hypothesis that a truly peripherally-restricted CB1 inhibitor, such as the MathMath, can effectively drive weight loss, but to also generate mechanistic data to support Scott's differentiated approach to CB1 inhibition. Recent biomarker analyses from our initial mouse DIO study has further extended the impact of the dose-dependent weight loss observed with the Mathemap treatment. Specifically, now we can report the Mathemap-dependent reduction in fasting insulin levels that complement significant glycemic control as well as productive modulation of key appetite-regulating hormones, including GLP-1 and leptin. Additional datasets also highlight significant reduction of inflammation in adipose tissue as well as liver steatosis. We are also happy to report that this initial study has now been repeated by an independent lab with very reproducible results, not only in terms of the magnitude of weight loss and body composition, that is preservation of lean mass with significant reduction of fat mass, but also with positive changes in glycemic control. This repeat study also looked carefully at food consumption and noted a significant reduction in cumulative caloric intake, slightly less but in line with semaglutide. Collectively, these studies highlight that namazumab-dependent efficacy is driven by multiple peripheral pathways coordinated through different organ systems. Building on our monotherapy studies, we compared namazumab, monluniband, a small molecule CB1 inhibitor, and the dual GLP-1 GIP agonist, terzepatide, both alone and in combination with namazumab, using our DIO model. We chose to use higher yet clinically translatable doses of CB1 inhibitors with the masinab having a similar level of exposure as the current phase 2 dose and monolunumab being slightly higher than its 20-day daily phase 2 dose. Those CD1 inhibitors demonstrated significant weight loss, over 23%, driven by reduced fat mass with lean mass preservation. We are encouraged that skies highly restricted in the masinab drove similar efficacy compared to the less peripherally restricted CD1 inhibitor monolunumab in a DIO model at clinically relevant doses. This study further highlighted that while an active yet suboptimal dose of transeptotide could yield a similar level of weight loss as namazumab, the combination with namazumab produced 31.5% weight loss. These results combined with our mechanistic data strongly support the potential for namazumab to be effective as both a monotherapy and as part of a combination approach to address the growing obesity epidemic. These in vivo studies continue to support our belief that our differentiated antibody approach can provide meaningful efficacy without the challenge that current small molecule inhibitors face, which is brain exposure that can cause unwanted neuropsychiatric side effects. To address this potential advantage, we ran a series of in vitro potency experiments designed to leverage a critical mechanistic difference between anathema and small molecule inhibitors. Unlike small-molecule CB1 inhibitors such as monoludivant that bind to the CB1 receptor at the orthosteric site, that is, the same site as the endogenous agonist, primarily the endocannabinoids AEA and 2-AG, the mass amount binds at the allosteric site and inhibits CB1 in a noncompetitive manner. We modeled a low concentration of CB1 agonist at 50 nanomolar, representing potential physiological conditions, where both drugs showed similar potency. However, when challenged with an elevated concentration at 2,000 nanomolars, mimicking a pathological state such as obesity, in which endocannabinoids become up-regulated, the mass amount potency remained remarkably stable while monolute events activity was significantly compromised. This differentiated mechanism has significant clinical implications. In obesity, where endocannabinoids can be greatly up-regulated, Small molecule CB1 inhibitors such as monolidibat may face increasing competition to bind to the receptor. This circumstance may potentially require higher doses of the small molecule inhibitor, which will increase brain exposure and the potential for neuropsychiatric risks. Conversely, nemacimab's allosteric binding avoids this competition, maintaining relatively similar potency regardless of endocannabinoid concentration. These data suggest that namazumab may offer the widest possible therapeutic window among CB1 inhibitors, potentially delivering significant metabolic benefits without having to navigate around the hurdle of neuropsychiatric side effects associated with achieving an appropriate peripheral exposure. We look forward to continuing our preclinical research efforts focused on further characterizing namazumab's differentiated and clinically relevant mechanism of action and having more data to share over the next month. Now, I'll turn the call over to our Chief Financial Officer, Caitlin Arsenault.